Details of the Drug Combination

General Information of Drug Combination (ID: DC1QRQG)

• Drug Combination Name: Aminosalicylic Acid + Maprotiline
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Aminosalicylic Acid (DMENSL5): Small molecular drug
  Maprotiline (DMPWB7T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.57
  Bliss Independence Score: 7.57
  Loewe Additivity Score: 8.52
  LHighest Single Agent (HSA) Score: 8.52

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Aminosalicylic Acid

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[3]
Pulmonary and extrapulmonary tuberculosis	1B10.Z	Approved	[3]
Pulmonary tuberculosis	1B10.Z	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]

Aminosalicylic Acid Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[5]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Modulator	[5]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Modulator	[5]

Aminosalicylic Acid Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3)	DTKWJH3	S38A3_HUMAN	Substrate	[6]

Aminosalicylic Acid Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[7]

Aminosalicylic Acid Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[8]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[8]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[8]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[8]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[8]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[8]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[8]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[8]
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Increases Acetylation	[9]

Indication(s) of Maprotiline

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[4]
Major depressive disorder	6A70.3	Approved	[3]
Mixed anxiety and depressive disorder	N.A.	Investigative	[4]

Maprotiline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[10]

Maprotiline Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[11]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]

Maprotiline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[12]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[13]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Aminosalicylic acid FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Maprotiline FDA Label
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem J. 2000 May 15;348 Pt 1:159-66.
• [7] Importance of the evaluation of N-acetyltransferase enzyme activity prior to 5-aminosalicylic acid medication for ulcerative colitis. Inflamm Bowel Dis. 2016 Aug;22(8):1793-802.
• [8] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [9] Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
• [10] Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
• [11] Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
• [12] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [13] The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.